Undifferentiated Spindle Cell Sarcoma Research Articles

Low-grade undifferentiated sarcoma with MEIS1::NCOA2-rearrangement primary to the lung: a case report

BackgroundMEIS1::NCOA2 is a rare fusion gene that has been recently described in a subset of spindle cell rhabdomyosarcomas and multiple low-grade undifferentiated spindle cell sarcomas predominantly arising in the genitourinary and gynecologic tracts with no specific line of differentiation. We present the first documented case of this neoplasm arising as a lung primary tumor.Case PresentationA 74-year-old woman with a 40-year smoking history presented with a 2.1 × 1.7 cm lung nodule discovered on computed tomography (CT) scan. A biopsy and subsequent lobe resection were performed, as well as an extensive metastatic work up, which revealed no additional masses. No specific line of differentiation was found by immunohistochemical staining, and an RNA-based fusion panel revealed a MEIS1::NCOA2 fusion, at which point a diagnosis of Low-Grade Undifferentiated Sarcoma with MEIS1::NCOA2-Rearrangement was rendered.ConclusionsThis report represents the first diagnosis of this tumor primary to the lung, and provides additional insight into the origin and localization of these rare tumors.

Superficial dedifferentiated liposarcoma: A clinicopathologic study

IntroductionDedifferentiation occurs in approximately 10% of atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLPS), primarily in retroperitoneal or deep-seated tumors, conferring metastatic potential. Superficial dedifferentiated liposarcoma (sDDLPS) is rare, and its progression and natural history are poorly documented. MethodsWe performed a 15-year retrospective review of our pathology database to identify cases of DDLPS in the skin or subcutaneous tissue. Diagnosis of primary sDDLPS required evidence of non-lipogenic sarcoma in the skin or subcutis, with concurrent ALT/WDLPS and/or MDM2 amplification. ResultsWe identified 14 cases of DDLPS involving skin or subcutis: 7 primary sDDLPS and 7 secondary lesions (3 from recurrent deep DDLPS and 4 from metastasis). Primary sDDLPS cases (4 females, 3 males; median age: 74) mainly presented as undifferentiated spindle cell or pleomorphic sarcoma. Tumor grades were grade 2 (5 cases) and grade 3 (2 cases), with three cases also showing grade 1 areas. MDM2 amplification was confirmed in 6 sDDLPSs for which FISH was successfully performed. Follow-up available for 6 sDDLPS patients showed 2 local recurrences, treated with re-excision and radiation therapy, with all disease-free at last follow-up (5–126 months). Of the 7 secondary cases, 2 had ongoing disease after multiple recurrences, 1 was disease-free, and all 4 with cutaneous metastasis died of disease (follow-up range: 24–263 months). ConclusionThese findings emphasize the importance of distinguishing between primary sDDLPS and secondary lesions due to their distinct prognoses. Metastasis or superficial extensions from deep DDLP correlate with a considerably worse prognosis than those originating in superficial tissues.

Jejunal Undifferentiated Spindle Cell Sarcoma with Intussusception Revealed by <sup>18</sup>F-FDG PET/CT

Jejunal Undifferentiated Spindle Cell Sarcoma with Intussusception Revealed by <sup>18</sup>F-FDG PET/CT

Malignant peripheral nerve sheath tumor (MPNST) and MPNST-like entities are defined by a specific DNA methylation profile in pediatric and juvenile population

BackgroundMalignant peripheral nerve sheath tumors (MPNSTs) account for 3–10% of pediatric sarcomas, 50% of which occur in neurofibromatosis type 1 (NF1). Sporadic MPNSTs diagnosis may be challenging due to the absence of specific markers, apart from immunohistochemical H3K27me3 loss. DNA methylation (DNAm) profiling is a useful tool for brain and mesenchymal neoplasms categorization, and MPNSTs exhibit a specific DNAm signature. An MPNST-like group has recently been recognized, including pediatric tumors with retained H3K27me3 mark and clinical/histological features not yet well explored. This study aims to characterize the DNAm profile of pediatric/juvenile MPNSTs/MPNST-like entities and its diagnostic/prognostic relevance.ResultsWe studied 42 tumors from two groups. Group 1 included 32 tumors histologically diagnosed as atypical neurofibroma (ANF) (N = 5) or MPNST (N = 27); group 2 comprised 10 tumors classified as MPNST-like according to Heidelberg sarcoma classifier. We performed further immunohistochemical and molecular tests to reach an integrated diagnosis. In group 1, DNAm profiling was inconclusive for ANF; while, it confirmed the original diagnosis in 12/27 MPNSTs, all occurring in NF1 patients. Five/27 MPNSTs were classified as MPNST-like: Integrated diagnosis confirmed MPNST identity for 3 cases; while, the immunophenotype supported the change to high-grade undifferentiated spindle cell sarcoma in 2 samples. The remaining 10/27 MPNSTs variably classified as schwannoma, osteosarcoma, BCOR-altered sarcoma, rhabdomyosarcoma (RMS)-MYOD1 mutant, RMS-like, and embryonal RMS or did not match with any defined entity. Molecular analysis and histologic review confirmed the diagnoses of BCOR, RMS-MYOD1 mutant, DICER1-syndrome and ERMS. Group 2 samples included 5 high-grade undifferentiated sarcomas/MPNSTs and 5 low-grade mesenchymal neoplasms. Two high-grade and 4 low-grade lesions harbored tyrosine kinase (TRK) gene fusions.By HDBSCAN clustering analysis of the whole cohort we identified two clusters mainly distinguished by H3K27me3 epigenetic signature. Exploring the copy number variation, high-grade tumors showed frequent chromosomal aberrations and CDKN2A/B loss significantly impacted on survival in the MPNSTs cohort.ConclusionDNAm profiling is a useful tool in diagnostic work-up of MPNSTs. Its application in a retrospective series collected during pre-molecular era contributed to classify morphologic mimics. The methylation group MPNST-like is a ‘hybrid’ category in pediatrics including high-grade and low-grade tumors mainly characterized by TRK alterations.

The efficacy of the TRK inhibitor entrectinib in patients with extracranial <i>NTRK</i> fusion-positive tumors

Somatic translocations involving the NTRK genes occur in 0.34–2.2% of all malignant neoplasms in children. TRK inhibitors whose efficacy has been demonstrated in prospective clinical studies expand treatment options for patients with solid tumors harboring NTRK gene rearrangements. The aim of our study was to summarize the first Russian experience with the use of the TRK inhibitor entrectinib in patients with extracranial NTRK fusion-positive solid tumors included in the compassionate use program. This study was approved by the Independent Ethics Committee and the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study included 8 patients who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and the N.N. Blokhin National Medical Research Center of Oncology. The main criteria for inclusion in the compassionate use program were a confirmed rearrangement of either NTRK1/2/3 genes in a solid tumor in patients with unresectable disease for whom no effective standard systemic therapy was available, progressive or recurrent disease during therapy prescribed according to the established diagnosis, risk group and risk stratification criteria, and the infeasibility of non-mutilating radical surgery. The median age at diagnosis was 4.3 months (range 1.2–83.6). The male to female ratio was 1:1. The primary site distribution was as follows: head and neck (n = 6; 75%), chest wall (n = 1; 12.5%), pelvis (n = 1; 12.5%). None of the patients had regional lymph node involvement or distant metastases at diagnosis. The distribution by histology (according to histopathology reports) was as follows: infantile fibrosarcoma (n = 4; 50%), undifferentiated round cell sarcoma, low-grade (n = 1; 12.5%), undifferentiated spindle cell sarcoma, high-grade (n = 1; 12.5%), NTRK-rearranged spindle cell sarcoma, low-grade (n = 1; 12.5%), spindle cell tumor associated with an NTRK rearrangement (n = 1; 12.5%). Immunohistochemistry (IHC) with a pan-Trk monoclonal antibody was performed in 7/8 (87.5%) patients. Pan-Trk IHC was positive in 4/7 (57%) patients. Rearrangements in the NTRK1 and NTRK3 genes were confirmed in all the patients. The final methods used for the detection of fusion transcripts were as follows: reverse transcription polymerase chain reaction (n = 4; 50%) and RNA-based next-generation sequencing (n = 4; 50%). NTRK1 and NTRK3 gene translocations were detected in 3/8 (37.5%) and 5/8 (62.5%) patients, respectively. The following fusion transcripts were identified: ETV6::NTRK3 (n = 4), DIP2C::NTRK3 (n = 1), TPR::NTRK1 (n = 1), TPM3::NTRK1 (n = 1), MYH10::NTRK1 (n = 1). One (12.5%) patient received entrectinib as first-line therapy, other patients (7/8, 87.5%) received entrectinib as secondor subsequent-line therapy. Three (37.5%) patients had undergone surgery before treatment with entrectinib: 2 had R2 resection, 1 had R0/R1 resection (resection margins were not evaluated). None of the patients received radiation therapy. The median duration of entrectinib therapy at the time of analysis was 11.8 months (range 2.3–20.1). Delayed surgery was performed in 2/8 patients; according to the histopathology reports, they achieved grade IV pathomorphosis. Three patients experienced adverse events during treatment with entrectinib. The median time to adverse events was 0.23 months (range 0.2–7.96). Three patients required temporary interruption in treatment to relieve symptoms, a subsequent dose reduction by one dose level was necessary when resuming therapy in two patients. The median follow-up since diagnosis was 19.5 months (range 14.9–75.0). All the patients included in our analysis were alive, three of them had no radiologic evidence of disease. Fifty percent of the patients completed targeted therapy, another 50% of the patients continued treatment with entrectinib. Complete and very good partial response was achieved in 3/8 and 2/8 patients, respectively. Partial response, minor partial response and stable disease were observed in one patient each. These results indicate high efficacy and safety of entrectinib in pediatric patients with extracranial NTRK fusion-positive solid tumors. Further studies are needed to determine the therapeutic potential of TRK inhibitors in the treatment of different solid malignant neoplasms in children and to assess long-term treatment results.

DCK expression by RNAseq as a potential biomarker of gemcitabine response in sarcoma.

11578 Background: Deoxycytidine kinase (DCK) is responsible for activation of gemcitabine by phosphorylation of gemcitabine to its monophosphate form. Studies have suggested that DCK expression may be correlated to response to gemcitabine in various solid tumors, and that downregulation of DCK may be at least partly responsible for gemcitabine-resistance in vitro. However, the significance of DCK expression in sarcomas as a biomarker of response to gemcitabine remains poorly characterized. Methods: Participants enrolled in the prospective Electronic Health Record (EHR)-Based Comprehensive Bone and Soft Tumor Registry ( NCT02677961 ) at The Ohio State James Cancer Center who had received gemcitabine-based chemotherapy for the treatment of bone and soft tissue sarcoma were eligible for this study. A total of 179 patients were identified who had received at least one cycle of gemcitabine-based chemotherapy, between January 1st, 2014, to December 31st, 2022. Whole exome RNASeq expression data was available for 36 of these patients who had received gemcitabine-based chemotherapy in the setting of active disease. Results: Of the 36 patients included in this study, 22 were female and 14 were male. Nine different main disease types were identified in the patient subset. These include angiosarcoma (8), chondrosarcoma (1), leiomyosarcoma (16), liposarcoma (3), malignant peripheral nerve sheath tumor (1), myxofibrosarcoma (2), osteosarcoma (2), undifferentiated pleomorphic sarcoma (3), and undifferentiated spindle cell sarcoma (1). The median time to treatment discontinuation (TTD) among all patients was 178 days. Among DCK low-expressors (n = 16), the median TTD was 86 days; among high-expressors (n = 16), the median TTD was not reached. Differences between groups did not reach statistical significance (HR = 0.55, p = 0.14). Conclusions: DCK expression by clinical RNASeq is a potential biomarker of gemcitabine-response in sarcoma, but larger studies are necessary to evaluate the potential clinical significance and possible role of DCK expression in identifying patients most likely to benefit from gemcitabine-based chemotherapy.

Intussusception caused by an extremely rare tumor: undifferentiated spindle cell sarcoma.

Intussusception caused by an extremely rare tumor: undifferentiated spindle cell sarcoma.

Rhabdomyosarcoma Arising in Inflammatory Rhabdomyoblastic Tumor: A Genetically Distinctive Subtype of Rhabdomyosarcoma

“Inflammatory rhabdomyoblastic tumor” (IRMT) is a recently coined name for a distinctive soft tissue neoplasm characterized by slow growth, a dense histiocytic infiltrate, scattered, bizarre-appearing tumor cells with morphologic and immunohistochemical evidence of skeletal muscle differentiation, a near-haploid karyotype with retained biparental disomy of chromosomes 5 and 22, and usually indolent behavior. There are 2 reports of rhabdomyosarcoma (RMS) arising in IRMT. We studied the clinicopathologic and cytogenomic features of 6 cases of IRMT with progression to RMS.Tumors occurred in the extremities of 5 men and 1 woman (median patient age, 50 years; median tumor size, 6.5 cm). Clinical follow-up (6 patients: median, 11 months; range 4-163 months) documented local recurrence and distant metastases in 1 and 5 of 6 patients, respectively. Therapy included complete surgical resection (4 patients) and adjuvant/neoadjuvant chemo/radiotherapy (6 patients). One patient died of disease, 4 were alive with metastatic disease, and one was without evidence of disease.All primary tumors contained conventional IRMT. Progression to RMS appeared as follows: (1) overgrowth of monomorphic rhabdomyoblasts with diminished histiocytes, (2) monomorphic spindle cell morphology with variably pleomorphic rhabdomyoblasts and low mitotic activity, or (3) morphologically undifferentiated spindle cell and epithelioid sarcoma. All but one were diffusely desmin-positive, with more limited MyoD1/myogenin expression. All RMS arising in IRMT, either primary or metastatic, demonstrated widespread loss of heterozygosity with retained heterozygosity of chromosomes 5 and 20, and all but one displayed additional gains and losses involving loci containing oncogenes/ tumor suppressor genes, most often CDKN2A and CDKN2B.RMS arising in IRMT have unique clinicopathologic and cytogenomic features, warranting classification as a distinct, potentially aggressive RMS subtype. It should be distinguished from other RMSs, particularly fusion-driven spindle cell RMS and pleomorphic RMS.

Left Kidney Undifferentiated Spindle Cell Sarcoma with Myeloid Cell Leukemia-1 Amplification: Therapeutic Response to Bortezomib, Venetoclax, and Dexamethasone Therapy

Abstract The overexpression of myeloid cell leukemia-1 (MCL-1) has been identified in numerous hematologic malignancies and solid tumors. Currently, there are no selective MCL-1 inhibitors. Here, we present a case of left kidney undifferentiated spindle cell sarcoma with MCL-1 amplification. The tumor showed primary resistance to chemotherapy and immune checkpoint inhibitors. Combination therapy of bortezomib, venetoclax, and dexamethasone demonstrated a positive response, resulting in a stable tumor condition for 6 months. To our knowledge, this is the first report to mention the clinical efficacy of bortezomib, venetoclax, and dexamethasone therapy in an MCL-1-amplified solid tumor.

Primary mediastinal spindle cell sarcoma in a dog

AbstractSoft tissue sarcomas are frequently reported tumours in dogs and are most often located in the cutaneous and subcutaneous tissues. Primary thoracic soft tissue sarcomas are infrequently reported in veterinary literature. This case report describes the diagnosis and treatment of a primary mediastinal spindle cell sarcoma of a 7‐year‐old, male, neutered Labrador retriever. Staging was performed before surgery. Computed tomography revealed a large intrathoracic mass in the left ventral hemithorax. A left‐sided thoracotomy was performed and a large pedunculated mass originating from the caudal mediastinum was excised. Histopathology revealed a high‐grade, undifferentiated spindle cell sarcoma. Immunohistochemistry staining confirmed the mesenchymal origin of the mass. Adjuvant chemotherapy was administered. Thoracic radiology was performed 38 days after surgery and revealed pleural effusion and mass effect in the caudal thorax. The patient was euthanased 66 days after surgery due to acute respiratory distress.

ARID1A deficient undifferentiated spindle cell and rhabdoid sarcoma of the prostate: report of a unique case with emphasis on diagnostic implications

BackgroundSWItch Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex functions collectively as a tumor suppressor and the inactivation of any of its constituent components is frequently associated with tumor initiation and/or progression. Most SWI/SNF deficient tumors share common rhabdoid morphology. ARID1A is the most frequently dysregulated SWI/SNF subunit in human cancer and inactivation of ARID1A is frequent across carcinomatous types while very rarely drives the tumorigenesis of sarcomas. Herein, we report a rare case of primary prostatic undifferentiated spindle cell sarcoma with focal rhabdoid morphology, harboring biallelic inactivation of ARID1A detected by next-generation sequencing with complete loss of ARID1A expression by immunohistochemistry.Case presentationThe patient is a 58-year-old man who presented with dysuria and obstructive voiding symptoms for 3 month and was found to have a large, ill-defined, prostatic mass lesion with circumferential extension into the rectal wall on imaging studies. A needle biopsy showed a spindle cell undifferentiated sarcoma of the prostate and the patient was treated by chemotherapy of combined etoposide and cisplatin for 2 months. A subsequent imaging study showed that the tumor was significantly enlarged, and the patient underwent laparoscopically radical prostatectomy. Gross examination showed a disrupted, 10 × 7 × 5 cm, solid and cystic mass involving almost the entire prostate and sparing the seminal vesicle glands. Histologic examination showed that tumor was composed mainly of mildly atypical, oval to spindle-shaped cells, arranged in sheets and fascicles or herringbone-like patterns within a small amount of edematous to myxoid, vascularized stroma. Notably, groups of discohesive rhabdoid tumor cells with eccentric nuclei, prominent nucleoli, and abundant globular cytoplasm were observed. There were prominent mitotic figures, multifocal geographic necroses, and foci of lymphovascular invasion. Immunohistochemistry showed that the tumor cells were diffusely positive for TLE-1 and vimentin and focally positive for epithelial membrane antigen, AE1/3, Cam5.2, SATB2, and CD34 (all in less than 10% tumor cells). Next-generation sequencing showed biallelic inactivation mutation of ARID1A; the predicted inactivating effect of ARID1A deletion was confirmed by immunohistochemical staining. After the surgery, the patient received an alternative combined chemotherapy of doxorubicin and ifosfamide for 5 months. The patient died 9 months after initial presentation due to extensive abdominal metastases.ConclusionsWe report an ARID1A deficient undifferentiated spindle cell and rhabdoid sarcoma of the prostate, adding to the growing spectrum of SWI/SNF driven undifferentiated sarcoma. Rhabdoid cells can be a helpful morphological clue for promoting molecular and immunohistochemical analyses for deficiency of SWI/SNF subunits, in the diagnostic workup of undifferentiated neoplasms featuring epithelioid or rhabdoid morphology.

Metastatic spindle cell sarcoma: A rare type of undifferentiated soft tissue neoplasm

Sarcomas are rare and characterised by an incidence of approximately 5 cases/100.000 people. Primary spindle cell sarcomas are a subclassification of soft tissue sarcomas, known as uncertain differentiation tumours, based on their unspecific line of differentiation. It might begin in layers of connective tissue under the skin, between muscles or surrounding organs. Diagnosis can be challenging and delayed due to the often-painless nature of these cancers and the common assumption of an underlying benign condition. The presence of distant metastatic disease at the time of the initial diagnosis is not frequent, but is more likely in large, deep and high-grade malignancy sarcomas. Our case describes an elderly patient diagnosed with an asymptomatic undifferentiated spindle cell sarcoma in the lower limb that developed metastatic disease after intentional curative therapy. Keywords: CT/MRI LI-RADS; CEUS LI-RADS; gadolinium contrast; MRI contrast agents; congenital heart disease; contrast enhanced ultrasound.

Management of Testicular Germ Cell Tumor With Somatic-Type Malignancy.

A man, aged 21 years, presented with a 4-month history of progressive swelling of the right testicle. Ultrasound revealed a heterogenous solid mass in the right testicle suspicious for malignancy. Further work-up included CT scans, which identified a 2-cm retroperitoneal lymph node; there was no evidence of thoracic metastases. Serum tumor markers revealed a mildly elevated α-fetoprotein (AFP) and normal lactate dehydrogenase (LDH) and human chorionic gonadotropin (hCG). The patient underwent right radical inguinal orchiectomy. Pathology evaluation demonstrated 1% teratoma with extensive secondary somatic-type malignant components of embryonal rhabdomyosarcoma and chondrosarcoma. No lymphovascular invasion was identified. Repeat tumor markers showed normal AFP, LDH, and hCG. Follow-up short-interval CT scans confirmed a dominant 2-cm interaortocaval lymph node with no evidence of distant metastases. The patient underwent retroperitoneal lymph node dissection, which revealed 1 of 24 lymph nodes positive for similar somatic-type malignancy composed of rhabdomyosarcoma and chondrosarcoma as well as undifferentiated spindle cell sarcoma with extranodal extension. Immunohistochemistry revealed that tumor cells were positive for myogenin and desmin and negative for SALL4.

Spermatocytic tumor of testis: A case series of 26 cases elucidating unusual patterns with diagnostic and treatment dilemmas.

Spermatocytic tumours are a rare subset of testicular tumours seen in elderly patients with distinct clinicopathological features and a favourable outcome. The typical presentation and characteristic histological features usually suffice for the diagnosis. Most of the cases are amenable to surgical excision. However, occasional cases which have a sarcomatous transformation may behave more aggressively and warrant adjuvant therapy. We present the clinicopathological features of a series of 26 cases diagnosed as Spermatocytic tumour at our tertiary cancer institute from 2002-2019. Twenty-four of these cases had the typical cytological features of a spermatocytic tumour while two cases showed sarcomatous change, one with rhabdomyosarcomatous differentiation and the other being an undifferentiated spindle cell sarcoma. Although the tumor can show varied patterns, the tripartite cytomorphology is typical in all cases. Careful note of these patterns and variations in histology is essential to prevent an erroneous diagnosis of other testicular neoplasms and guide the therapy.

Dedifferentiated liposarcoma of the spermatic cord: A case report

Introduction: Soft tissue sarcomas account for and #60;1% of all adult malignancies with the most commonly reported being liposarcomas, leiomyosarcomas, or rhabdomyosarcomas. Genitourinary tract (GU) sarcomas are considered as an even more rare subtype of soft tissue sarcomas. A patient who presented with a unilateral painless mass initially diagnosed as a high-grade undifferentiated spindle cell neoplasm most consistent with sarcoma by intralesional excisional biopsy found to be a primary undifferentiated spindle cell sarcoma arising from the left-sided spermatic cord. Final diagnosis after radical resection of the mass was dedifferentiated liposarcoma most likely arising from the spermatic cord. After resection of the mass, the patient was diagnosed with a dedifferentiated liposarcoma most likely arising from the spermatic cord. There is sparse literature on this type of spermatic cord sarcoma. The goal of this case report is to summarize the findings that led to this rare diagnosis. Case Report: This is the case of an 81-year-old white male who presented to his primary care physician due to a mass in his left groin. After initial clinical misdiagnosis and mismanagement, the patient underwent incisional biopsy and was diagnosed with a stage IIIB, cT3 N0 M0 primary undifferentiated spindle cell sarcoma of the left-sided spermatic cord, grade 3. Upon radical resection, the final diagnosis was high grade dedifferentiated liposarcoma measuring 8.8 × 5.0 × 4.8 cm. Conclusion: There is currently a paucity of literature on dedifferentiated liposarcomas arising from the spermatic cord. The patient was initially diagnosed with an undifferentiated spindle cell sarcoma thought to have arisen from the spermatic cord, however, upon undergoing radical resection, the final diagnosis was determined to be a high grade dedifferentiated liposarcoma. This case discusses the rare diagnosis of a dedifferentiated liposarcoma most likely arising from the spermatic cord. It is believed that clinicians should consider malignancy in the differential diagnosis of patients presenting with an inguinal mass.

The value of re-staging chest CT at first local recurrence of extremity and trunk soft tissue sarcoma

To determine the prevalence of pulmonary metastases on re-staging chest CT at the time of first local recurrence (LR) of trunk or extremity soft tissue sarcoma (STS). Retrospective review of all patients diagnosed with recurrent STS between May 2007 and April 2018. Data collected included patient age and sex, site of primary STS, time to LR, recurrence site, initial tumour grade, recurrent tumour grade, findings of initial staging chest CT, and prevalence of pulmonary metastases on re-staging chest CT. The study included 109 patients (males = 68, females = 41; mean age 56years, range 9-92years). The commonest tumour sub-types were myxofibrosarcoma (27.5%), undifferentiated pleomorphic/spindle cell sarcoma (20.2%), synovial sarcoma (10.1%), and malignant peripheral nerve sheath tumour (10.1%). Initial staging chest CT demonstrated pulmonary metastases in 1 of 77 (1.3%) patients for whom CT was available for review. The mean time to LR was 30.8months (range 3-224months). Pulmonary metastases were diagnosed on re-staging chest CT in 26 of 109 cases (23.9%), being commonest with grade 3 STS (36.1%). Pleomorphic sarcoma (85.7%) and undifferentiated spindle cell sarcoma (33.3%) were the 2 commonest tumour sub-types associated with pulmonary metastases at first LR. Re-staging chest CT at the time of first LR of STS identified a prevalence of 23.9% pulmonary metastases, which supports the need for chest CT at the time of LR in line with the UK guidelines for the management of bone and soft tissue sarcoma. • Pulmonary metastases were diagnosed in 1.3% of soft tissue sarcomas at presentation. • Pulmonary metastases were identified in ~ 24% of patients at first local recurrence of soft tissue sarcoma, most commonly with pleomorphic sarcoma and Trojani grade tumours. • No patient with a low-grade recurrence had pulmonary metastases.

ATYPICAL SPINDLE CELL NEOPLASM OF THE JAW MIMICKING A BENIGN LESION—A RARE CASE REPORT

Clinical Presentation Atypical spindle cell neoplasms are extremely rare lesions, especially in the jaws, and are well known for their aggressive behavior.1 We present the case of a 58-year-old male in whom this tumor was incidentally noted on routine dental examination. The tumor resembled a benign odontogenic lesion on computed tomography (CT) and magnetic resonance imaging (MRI). Because of its propensity for metastasis, positron emission tomography (PET)/CT was performed to rule out distant metastasis. Differential Diagnosis Correlating the innocuous clinical presentation with the radiographic appearance of well-defined nature of the lesion and its paracoronal position with respect to an impacted tooth, the differential diagnosis included dentigerous cyst, other odontogenic cyst, cystic ameloblastoma, and other benign odontogenic tumor. Because of the irregular margins, we assumed the lesion could have been secondarily infected. Diagnosis and Management Histopathologic examination revealed an atypical pleomorphic spindle cell neoplasm of indeterminate origin. The patient underwent segmental mandibulectomy with radical neck dissection. Follow-up PET/CT revealed mild fluoro-2-deoxy-D-glucose (FDG) avidity in the left intraparotid lymph nodes. This could be a reactive process or recurrent/second primary tumor. A close follow-up after 3 months was recommended. Discussion Undifferentiated spindle cell sarcomas are high-grade, aggressive soft tissue sarcomas with no specific line of differentiation. To our knowledge, fewer than 30 cases have been reported. This case would be of specific interest to oral and maxillofacial radiologists because of its resemblance to a benign odontogenic lesion on CT and MRI. In conclusion, this malignancy can mimic benign lesions, and this may have significant influence on formulating the treatment plan, favoring a more conservative approach. Atypical spindle cell neoplasms are extremely rare lesions, especially in the jaws, and are well known for their aggressive behavior.1 We present the case of a 58-year-old male in whom this tumor was incidentally noted on routine dental examination. The tumor resembled a benign odontogenic lesion on computed tomography (CT) and magnetic resonance imaging (MRI). Because of its propensity for metastasis, positron emission tomography (PET)/CT was performed to rule out distant metastasis. Correlating the innocuous clinical presentation with the radiographic appearance of well-defined nature of the lesion and its paracoronal position with respect to an impacted tooth, the differential diagnosis included dentigerous cyst, other odontogenic cyst, cystic ameloblastoma, and other benign odontogenic tumor. Because of the irregular margins, we assumed the lesion could have been secondarily infected. Histopathologic examination revealed an atypical pleomorphic spindle cell neoplasm of indeterminate origin. The patient underwent segmental mandibulectomy with radical neck dissection. Follow-up PET/CT revealed mild fluoro-2-deoxy-D-glucose (FDG) avidity in the left intraparotid lymph nodes. This could be a reactive process or recurrent/second primary tumor. A close follow-up after 3 months was recommended. Undifferentiated spindle cell sarcomas are high-grade, aggressive soft tissue sarcomas with no specific line of differentiation. To our knowledge, fewer than 30 cases have been reported. This case would be of specific interest to oral and maxillofacial radiologists because of its resemblance to a benign odontogenic lesion on CT and MRI. In conclusion, this malignancy can mimic benign lesions, and this may have significant influence on formulating the treatment plan, favoring a more conservative approach.

Primary undifferentiated spindle cell sarcoma obstructing the right ventricular outflow tract

BackgroundPrimary undifferentiated spindle cell sarcoma in the right ventricle is an extremely rare tumor. Radical surgical excision is the optimal treatment for long-term survival due to poor response to chemotherapy or radiotherapy at an advanced stage.Case presentationA 42-year-old man with no previous medical history presented with mild dyspnea on exertion and abdominal distension that lasted a week. Computed tomography (CT) revealed a huge homogeneous mass completely obstructing the right ventricle and extending into the pulmonary trunk. However, he suddenly collapsed the next day while on his way to an echocardiography. An extracorporeal membrane oxygenation (ECMO) device was inserted percutaneously and ECMO support was urgently initiated. Based on consideration of right ventricular outflow tract (RVOT) obstruction in the initial CT scan, we decided to remove the mass from the right ventricle immediately. The main mass was resected to relieve the RVOT obstruction, and after the operation, the ECMO was removed from the operation room. However, the patient failed to regain consciousness and electroencephalography (EEG) and subsequent magnetic resonance imaging (MRI) indicated severe hypoxic brain damage. We assume CPR was unsuccessful because the mass completely blocked the RVOT. Pathology revealed the mass was an undifferentiated spindle cell sarcoma.ConclusionsWe present the case of a 42-year-old male with cardiac arrest due to right ventricular outflow tract obstruction by a tumor of the right ventricle. Surgical resection was performed and in histopathology it was proved to be an undifferentiated spindle cell sarcoma.

Undifferentiated Spindle Cell Sarcoma in the Retroperitoneum- Case Report

Undifferentiated Spindle Cell Sarcoma in the Retroperitoneum- Case Report

Immune signature and molecular profiling of radiation-induced sarcoma (RIS).

11040 Background: RIS is a rare subset of soft tissue sarcoma (STS) with poor prognosis and limited treatment options. We hypothesize that subsets of STS that carry genomic complexity, such as RIS, will have a neoepitope and immune signature that predicts response to immunotherapy as these mutations act as strong antigenic targets for eliciting immune response. Methods: Cases of RIS were identified from an institutional database. Formalin fixed paraffin embedded (FFPE) samples were stained for PD-1, PD-L1, CD3, CD4, CD8. Immune scoring was performed. Tumor-infiltrating lymphocytes (TILs) were assessed using a 4-tiered scale: 0 (no lymphocytes); 1 (1-10/HPF); 2 (11-50/HPF), 3 (51-100/HPF); 4 ( > 100/HPF). TIL staining with PD-1 and PD-L1 was also scored whereby the overall percentage of positive cells on the entire slide was quantified. Tumor DNA was extracted from FFPE samples and underwent whole exome sequencing (WES). Results: FFPE samples from 20 cases of RIS were selected for analysis. PD-1 and PD-L1 expression (threshold set at ≥ 1% positive cells) was seen in 35% and 45% of the cases respectively. CD3+, CD4+, CD8+ T cell infiltration (threshold set ≥ 11 cells /HPF) was seen in 45%, 15% and 20% of cases respectively. 12 exomes of unpaired RIS samples were successfully sequenced. The most common histologies were angiosarcoma (n = 3), undifferentiated spindle cell sarcoma (n = 3), de-differentiated liposarcoma (n = 2) and radiation induced spindle cell sarcoma (n = 2). Provisional analysis did not reveal any pattern to the relative mutational burden between the RIS’s. There does however seem to be relatively higher rate of mutation than that seen in other cancer subtypes. Half the samples had at least one pathogenic or likely pathogenic variant. Different HRAS mutations were seen in two samples (sarcoma NOS and angiosarcoma) and FGFR4 mutation was present in two samples, both spindle cell sarcomas. Conclusions: To our knowledge this is the first study to investigate the immune profile in RIS. Up to 45% of these tumors were positive for PD1/PDL1 expression, as well as presence of tumour infiltrating lymphocytes. Results from WES demonstrate that RIS may benefit from immunotherapy due to a relatively higher mutational burden.